Very little is known about what determines sex differences in the development of hypertension. This group has clearly delineated in the past that there is a gene on the Y chromosome that influences blood pressure in male WKY rats. This proposal looks at an interesting effect in which transferring the X chromosome from a male WKY SHRy congenic strain to WKY rats still alters blood pressure and the expression of components of the renin-angiotensin system even though female WKY and WKY SHRy rats should be genetically identical. The working hypothesis is that there may be differences in the imprinting of the X chromosome in the two strains that affects expression of a gene that regulates other genes that affect blood pressure. This is a very novel idea, the exploration of this hypothesis is only made possible by the availability of a unique congenic strain of rats in Akron. The proposed studies could have important impact on genetic research of polygenic diseases since it indicates that single sex genetic crosses may miss important gene/gene interactions and that there may be important disease-producing genes that do not exhibit sequence variants in either the coding or promoter regions of genes.